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Type I, II, III, and IV collagen is found in which tissues?
I: skin, bone, tendon, vasculature, cornea (mechanical stability, resistance to tension)
II: cartilage, vitreous-body, vertebral disk (tensile strength)
III: vasculature, organs, skin (flexibility)
IV: basement membrane (support)
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Collagen chain repeat consists of?
Gly-X-Y (X = proline, Y = hydroxylproline, hydroxylsine)
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Each collagen chain forms a ____-handed helix bit the landmark structure forms a ____-handed helix from h-bonding
Left; right
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synthesized in RER as ____ and signal peptide is cleaved to make _____
pre-pro-alpha chain; pro-collagen
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What do prolyl and lysyl-hydroxylase + ascorbate do?
Where?
- In RER, hydroxylproline and hydroxylysine are produced via these enzymes (this is UNIQUE to collagen)
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Hydroxylysine on the end chains of pro-peptide are _______ to add _____ or ____ which increases turnover rate.
O-glycosylated; galactose or glucosyl-galactose
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Intermolecular di-sulfide bonds are formed by? Where are these bonds formed? Intracellularly or extracellularly?Purpose?
- protein disulfide isomerase (oxidates cystein residues);
- in C-terminus extension;
- Within the cell;
- permit H-bonding and triple helix formation
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Procollagen peptidases do what?
cleace N, C termini extensions to give tropocollagen which associate in parallel array 3/4 length overlap
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What fills the gap regions of 3/4 length overlap of tropocollagen fibrils?
CaPO4 in bone formation
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what does lysyl-oxidase do? Why?
oxidatively deaminates hydroxylysyl and lysyl residues to form aldehydes (allysine/hydroxyallysine)
aldehydes of adjacent tropocollagens stabilze fibrils (via condensation)
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In biosynthesis of collagen, where does each step occur?
- Intracellular:
- 1. removal of pre-peptide (i.e. signal peptide)
- 2. hydroxylate pro/lys residues via prolyl or lysyl-hydroxylase (i.e. cytosolic enzymes)
- 3. glycosylate hydroxylysine on end chain
- 4. oxidation of cys (i.e. formation of S-S bonds)
- 5. assembly of 3 peptides to form triple helix
exocytosis
- Extracellular:6. removal of the pro-peptide (i.e. N,C extensions)
- 7. staggered (3/4 length overlap) to form fibrils
- 8. gap junctions filled with CaPO4
- 9. Oxidation of hydroxylysyl and lysine residues to aldehyde form
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Different types of Ehler's-Danlos syndrome?
Stretchy skin and loose joints.
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Osteogenesis imperfecta?
group of disorders in which bone bends and easily fracture due to defective collagen 1 resulting from mutation in the collagen repeat that prevents helix formation (i.e. gly for bulky amino acid)
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scurvy?
vit. c deficiency prevents hydroxylation of pro/lys residues such that h-bonding cannot occur in pro-collagen
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marfan syndrom?
NOT a collagen based disease. It's elastin (or fibrillin) based.
caused by mutation in fibrillin gene
long fingers, arms, legs
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thrombosis?
platelets bind to type IV collagen on basal lamina
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Neoplasms?
breast tumors where proliferation of fibroblasts continue to lay down type I collagen to make tumor palpale
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metastasis?
tumors enter blood stream
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elastin has ___-like qualities and found in?
rubber-like, vasculature
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Elastin is hydro phobic or philic?
hydrophobic and contains small, non-polar AA (GAV)
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Elastin cross-links into irregular networks by which AA?
short stretches of Lysine, X, Y (X=y=non polar AA like alanine)
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Desmosine?
unique 4-residue cross-links of elastin; uses lysyl oxidase (creates allysel residues)
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fibrillin?
elastin fibers covered with glycoproteins
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elastin vs. collagen in:
turn over rate and genes that create them? Shared enzymes?
- elastin is most stable protein in body (slowly turned over)
- elastin is made from ONE gene; collagen from many genes
shared enzyme: lysyl oxidase
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What are GAGs?
large, unbrached neg. charged polysaccharide chains associated with protein core
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How do GAGs attach to protein core?
protein core (ser or thr) attached to linker tri-sacc. (Gal-Gal-Xyl) which is attached to acidic sugar (negative)-amino sugar (neutral) repeat.
*negative charges allow sacc. chains to repel each other (looks like test tube cleaner)
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Proteoglycan aggregate?
PG reacting with hyaluronic acid to create this. Can absorb compressive forces, spring back b/c of neg. charges
**allows for flexibility/compressibility of collagen fibers (ear)
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GAGs lubricating properties are related to mucous secretions and prevalent in ____?
cartilage and synovial fluid
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dynamic remodeling of connective tissue is indicative by?
increased detection of hydroxylysin/hydroxylproline in ruine 2 days after exercise
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lysosomal storage disease?
lysosomes hold many acid hydrolases that degrade GAGs..many deficiences are characterized by missing one or more enzyme required to degrade GAGs
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how can you test lysosomal storage diseases?
check urine for presence of characteristic oligosaccharides
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Fibronectin? Vitronectin? Laminin?
fibronectin: group of proteins that interact with cell surface proteins (integrins)
vitronectin: fibronectin in localized areas of tissue injury
laminin: attach to basal lamina
**cell adhesion to fibronectin/laminin can promote growth, migration
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where does proteoglycan synthesis occur (in or out of cell)?
In cell (RER --> golgi)
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What are the six proteoglycans?
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